Question

Toxicity of LSD Dissociative anesthetic Relationship between lupus solubility and potency of opioids

Answer 1

Hallucinogens :

Hallucinogens are a class of drugs that cause hallucinations—profound distortions in a person’s perceptions of reality. Hallucinogens can be found in some plants and mushrooms (or their extracts) or can be man-made, and they are commonly divided into two broad categories: classic hallucinogens (such as LSD) and dissociative drugs (such as PCP). When under the influence of either type of drug, people often report rapid, intense emotional swings and seeing images, hearing sounds, and feeling sensations that seem real but are not.

While the exact mechanisms by which hallucinogens and dissociative drugs cause their effects are not yet clearly understood, research suggests that they work at least partially by temporarily disrupting communication between neurotransmitter systems throughout the brain and spinal cord that regulate mood, sensory perception, sleep, hunger, body temperature, sexual behavior, and muscle control.

Dissociative Drugs

PCP (Phencyclidine)—also known as ozone, rocket fuel, love boat, hog, embalming fluid, or superweed.

PCP can be snorted, smoked, injected, or swallowed. It is sometimes smoked after being sprinkled on marijuana, tobacco, or parsley.

                  

Ketamine—also known as K, Special K, or cat Valium—is a dissociative currently used as an anesthetic for humans as well as animals. Much of the ketamine sold on the street has been diverted from veterinary offices. Although it is manufactured as an injectable liquid, ketamine is generally evaporated to form a powder that is snorted or compressed into pills for illicit use. Because ketamine is odorless and tasteless and has amnesia-inducing properties, it is sometimes added to drinks to facilitate sexual assault.

                                          

Salvia divinorum—also known as diviner’s sage, Maria Pastora, Sally-D, or magic mint—is a psychoactive plant common to southern Mexico and Central and South America. Salvia is typically ingested by chewing fresh leaves or by drinking their extracted juices. The dried leaves of salvia can also be smoked or vaporized and inhaled.

LSD (d-lysergic acid diethylamide)—also known as acid, blotter, doses, hits, microdots, sugar cubes, trips, tabs, or window panes—is one of the most potent mood- and perception-altering hallucinogenic drugs. It is a clear or white, odorless, water-soluble material synthesized from lysergic acid, a compound derived from a rye fungus. LSD is initially produced in crystalline form, which can then be used to produce tablets known as “microdots” or thin squares of gelatin called “window panes.” It can also be diluted with water or alcohol and sold in liquid form. The most common form, however, is LSD-soaked paper punched into small individual squares, known as “blotters.”

Psilocybin(4-phosphoryloxy-N,N-dimethyltryptamine)—also known as magic mushrooms, shrooms, boomers, or little smoke—is extracted from certain types of mushrooms found in tropical and subtropical regions of South America, Mexico, and the United States. In the past, psilocybin was ingested during religious ceremonies by indigenous cultures from Mexico and Central America. Psilocybin can either be dried or fresh and eaten raw, mixed with food, or brewed into a tea, and produces similar effects to LSD.

Peyote (Mescaline)—also known as buttons, cactus, and mesc—is a small, spineless cactus with mescaline as its main ingredient. It has been used by natives in northern Mexico and the southwestern United States as a part of religious ceremonies. The top, or “crown,” of the peyote cactus has disc-shaped buttons that are cut out, dried, and usually chewed or soaked in water to produce an intoxicating liquid. Because the extract is so bitter, some users prepare a tea by boiling the plant for several hours. Mescaline can also be produced through chemical synthesis.

*In this report, the term “hallucinogen” will refer to the classic hallucinogenic drugs LSD and Psilocybin.

Opioids:

Morphine is commonly considered to be the archetypal opioid analgesic and the agent to which all other painkillers are compared. There is evidence to suggest that as long ago as 3000 bc the opium poppy, Papaver somniferum, was cultivated for its active ingredients. It was, however, not until morphine was isolated from opium in 1806 by Sertürner that modern opioid pharmacology was truly born. In 1847 the chemical formula for morphine was deduced and this, coupled with the invention of the hypodermic needle in 1853, led to the more precise and widespread clinical use of morphine

Opioids can also be classified according to their effect at opioid receptors. In this manner opioids can be considered as agonists, partial agonists and antagonists. Agonists interact with a receptor to produce a maximal response from that receptor (analgesia following morphine administration is an example). Conversely, antagonists bind to receptors but produce no functional response, while at the same time preventing an agonist from binding to that receptor (naloxone). Partial agonists bind to receptors but elicit only a partial functional response no matter the amount of drug administered (buprenorphine).

Classification of opioids by synthetic process.

Naturally occurring compounds	Semi-synthetic compounds	Synthetic compounds
Morphine	Diamorphine (heroin)	Pethidine
Codeine	Dihydromorphone	Fentanyl
Thebaine	Buprenorphine	Methadone
Papaverine	Oxycodone	Alfentanil
		Remifentanil
		Tapentadol

Opioids From Higher Strength to Lower:

list of some of the more widely-known opioids drugs:

• Opium
• Heroin
• Codeine
• Oxycodone
• Hydrocodone
• Tramadol
• Morphine
• Hydromorphone
• Fentanyl
• Carfentanil

1.Fentanyl

Fentanyl is a synthetic opioid that is 30-50 times more potent than heroin. Fentanyl is a prescription drug generally prescribed for patients to manage severe pain after surgery. Common brand names for Fentanyl include Actiq, Duragesic, and Sublimaze. It may also be prescribed for patients with chronic pain who have built a physical tolerance to other opioids.

2.Heroin

Heroin, the second strongest opioid, is a semi-synthetic opioid derived from morphine, a natural substance that comes from the poppy plant. Heroin is the only illegal drug included in this list, as most opioids serve a medicinal purpose, whereas Heroin does not.

Heroin is also the only schedule I drug on the list, and has a very strong potential for abuse. It is used by injecting, snorting, or smoking, and is often found as a white or black powder, or a black sticky substance.

3.Hydromorphone

Hydromorphone is another strong opioid that is 2 to 8 times more potent than morphine. Prescribed as a severe pain reliever in the brand name Dilaudid, Hydromorphone produces feelings of sedation and relaxation.

4.Oxymorphone

Although fourth on the list, Oxymorphone is a very strong opioid. Found in the brand name Opana, Oxymorphone is prescribed to treat moderate to severe pain. It generally comes in tablet form, but is sometimes prescribed as an injectable solution.

5.Methadone

While Methadone is used under strict medical supervision to treat addiction or painful symptoms of withdrawal, nonmedical use is illegal. Methadone is chemically dissimilar to Heroin and Morphine, but still produces similar effects of euphoria and sedation.A potent opioid analgesic that is well absorbed with good oral bioavailability (75%).

However, its main use is as a substitute for opioids, for example diamorphine (heroin) in addicts because its slow onset and offset reduces the incidence of withdrawal symptoms. It is itself addictive.

6.Oxycodone

While Oxycodone isn’t as strong as the above opioids, it is still considered a schedule II drug with high potential for abuse and dependence.

7.Morphine

Morphine is the only natural opiate (non-synthetic opioid) on the list, but is included because the potency of opioids are often compared to Morphine. Often prescribed to treat pain when other opioids are ineffective, Morphine is similar in potency to Oxycodone.

8.Hydrocodone

Hydrocodone is near equipotent to morphine, and is generally prescribed to treat moderate pain. Some brand names for Hydrocodone include Vicodin, Lortab, and Hycodan. More potent than Codeine, Hydrocodone is the most frequently prescribed opioid in the United States, with a staggering 136 million prescriptions filled in the first several months of 2014.

9.Codeine

Codeine is weaker in potency, and is generally prescribed to treat mild to moderate pain, and may be used with other medications to reduce coughing.

10.Tramadol

Tramadol has similar potency to Meperidine, but, as a schedule IV drug, has less potential for physical dependence, tolerance, and abuse. However, Tramadol, or brand name Ultram, can still be abused by those suffering from addiction or chronic pain.

Anesthesia:

Opioids are frequently used as premedicant drugs before anesthesia and surgery because of their sedative, anxiolytic, and analgesic properties. In addition, these agents are used intraoperatively both as adjunctive therapy and in high doses as a major component of the anesthetic protocol.Opioids are often used as regional analgesics and administered into the epidural or subarachnoid spaces of the spinal cord. 2 Opioids are also commonly utilized during cardiac and other types of highrisk surgery to minimize cardiovascular depression.

Effects of Lipid Solubility on Drug Behavior

We normally think of fentanyl as short-acting and morphine as long-acting. However, the 2 drugs have similar elimination half-lives: 2-4 hours for morphine and 3-7 hours for fentanyl. We often think of drug elimination as determining the duration of effect. However, morphine does not last longer than fentanyl because it is eliminated more slowly from the body; it lasts longer because once it enters the central nervous system it has a difficult time exiting the cellular lipid barrier (blood-brain barrier). It is this retention in the central nervous system that makes morphine longer-acting than fentanyl. Because morphine is not very lipid-soluble, it takes a long time to cross the blood-brain barrier both going into and out of the brain. This produces what one might call a "slow-in, slow-out" drug. Indeed, when compared with lipid-soluble drugs, morphine is noted to be slower in onset. Fentanyl, on the other hand, is lipophilic and crosses the blood-brain barrier rapidly in both directions; it is a "fast-in, fast-out" drug. Therefore, fentanyl acts quickly and has a short duration of action because of its lipid solubility.

Another factor that can play a role in how a drug behaves clinically is receptor affinity. If an opioid binds tightly to a mu receptor, it may have a surprisingly long duration of action. The mu receptor dissociation constant for fentanyl is 1.9 and 2.0 for morphine, indicating that they are very similar. Because their elimination half-lives, as described above, and their mu receptor binding affinities are very similar, it is primarily differences in lipid solubility that govern the different behaviors of these 2 drugs.